Etiology and Pathogenesis

The cervical lymphatic system consists of a collection of both superficial and deep lymph nodes that protect the head, neck, nasopharynx, and oropharynx against infection (Figure 87-1). Lymph nodes can enlarge by either proliferation of normal cells intrinsic to the node such as lymphocytes or infiltration by cells extrinsic to the node such as neutrophils or malignant cells. The most common cause of cervical lymphadenopathy in children is reactive intranodal hyperplasia secondary to infection. The majority of lymphatics of the head and neck drain to the submandibular lymph nodes and the anterior and posterior cervical lymph node chains. Consequently, these nodes are involved in most children with cervical lymphadenitis.

Figure 87-1 Lymph vessels and nodes of head and neck.

Many different organisms have been implicated in cervical lymphadenitis (Box 87-1). The most common cause of cervical lymphadenitis is viruses that infect the upper respiratory tract, including adenovirus, respiratory syncytial virus, influenza, and parainfluenza. When bacterial in origin, cervical lymphadenitis may be a primary process or result from direct extension of a local infection such as pharyngitis or dental abscess. In the case of acutely inflamed and enlarged unilateral nodes, aspirates reveal infection by Staphylococcus aureus or Streptococcus pyogenes (group A β-hemolytic streptococci [GABHS]) in the majority of cases. Recent studies of suppurative lymphadenitis show the predominance of S. aureus and the increased prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA). More indolent causes of cervical lymphadenitis include Bartonella henselae, mycobacterial infections, and Toxoplasma gondii. The age of a child plays a role in predicting the infectious etiology of cervical lymphadenitis (Table 87-1).

Table 87-1 Etiology of Cervical Lymphadenitis by Age Group

Clinical Presentation and Differential Diagnosis

The presentation of cervical lymphadenitis can be divided into three broad categories: (1) acute bilateral, (2) acute unilateral, and (3) subacute or chronic. The most common causes of acute bilateral cervical lymphadenitis are viral upper respiratory tract infections followed by pharyngitis caused by GABHS. In general, the lymph nodes are small, soft, and mobile without associated erythema, warmth, or significant tenderness. Additional clinical features such as gingivostomatitis in herpes simplex virus or pharyngoconjunctival fever caused by adenovirus may help to identify the causative virus. Viral causes of generalized lymphadenopathy, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), can cause acute bilateral cervical lymphadenitis associated with infectious mononucleosis. In both cases, posterior cervical lymph node enlargement is most prominent followed by anterior cervical nodes.

Acute unilateral cervical lymphadenitis is caused by S. aureus and S. pyogenes in the majority of cases. The onset may be associated with an upper respiratory tract infection, pharyngitis, or periodontal disease, and associated fever is common. Typically, the onset is acute with development of large, tender, erythematous, and warm lymph nodes that may become fluctuant over a few days (Figure 87-2). In addition, a cellulitis–adenitis syndrome caused by group B streptococcus in infants between 3 and 7 weeks of age is associated with irritability, fever, and unilateral facial or submandibular swelling with erythema and tenderness.

Figure 87-2 Cervical lymphadenitis.

The most common causes of subacute or chronic lymphadenitis are mycobacterial infections, cat scratch disease, and toxoplasmosis. Lymph node enlargement is typically gradual in onset and progresses over weeks to months. The most common presentation of nontuberculous mycobacterium (NTM) disease in children is cervical lymphadenitis. The lymph nodes are large and indurated but nontender, and the overlying skin often becomes violaceous and thin (see Figure 87-2). Untreated lymphadenitis caused by NTM may resolve, but often it progresses to lymph node necrosis followed by fluctuance and spontaneous drainage. Cervical lymphadenitis caused by Mycobacterium tuberculosis has a similar presentation, but there are clinical and epidemiologic differences. NTM is uncommon in children older than 5 years of age compared with tuberculosis, which can occur at any age. With NTM, involvement is usually unilateral and associated with a normal chest radiograph and a normal or minimally indurated purified protein derivative (PPD). In contrast, children with tuberculous cervical lymphadenitis are more likely to have bilateral lymph node involvement, systemic symptoms, an abnormal chest radiograph, and an abnormal PPD result.

Cat-scratch disease, caused by B. henselae, most commonly affects the axilla and cervical regions. Most patients have a history of recent contact with cats or kittens. Clinical manifestations begin with a papule or pustule that develops at the inoculation site a few days to weeks after a bite or scratch followed by lymphadenitis proximal to the site. Lymphadenitis is tender and erythematous and often associated with fever. Lymphadenitis typically persists for several weeks to months and may suppurate. Acquired Toxoplasma infection, when symptomatic, generally presents as cervical lymphadenopathy and fatigue without fever. Lymphadenitis most frequently involves a solitary node in the head and neck region without systemic symptoms. Lymphadenitis secondary to toxoplasmosis tends to be nonsuppurative and may persist for many months. In addition, viral etiologies such as EBV, CMV, and HIV can cause bilateral subacute cervical lymphadenitis.

Noninfectious causes of lymphadenitis in children are less common but should always be considered in the differential diagnosis. Congenital cysts such as branchial cleft cysts, cystic hygromas, and thyroglossal duct cysts can mimic lymphadenitis, especially when infected. Malignancies such as lymphoma, leukemia, neuroblastoma, and rhabdomyosarcoma can present as cervical lymphadenopathy. Malignancy should be considered in cases of indolent lymphadenopathy, especially with a history of weight loss, fevers, night sweats, or lymphadenitis that is unresponsive to antibiotic treatment. Other causes of cervical neck masses should be included in the differential diagnosis of cervical lymphadenitis (Box 87-2).

Evaluation and Management

Lymphadenitis is a clinical diagnosis based on physical examination findings of enlarged and inflamed palpable lymph nodes. The evaluation and management of cervical lymphadenitis is directed by a thorough history and physical examination. Patients with acute small, bilateral nodes with minimal tenderness along with symptoms of fever or respiratory tract infection most likely have a viral syndrome and can be managed conservatively with observation and supportive care. If GABHS pharyngitis is suspected, a rapid streptococcal antigen test or throat culture should be performed. In patients with acute large, unilateral, erythematous, and tender nodes associated with fever, bacterial infection is most likely. Antimicrobial therapy should be directed at S. pyogenes and S. aureus with cephalexin being a reasonable choice. Because of the continuing rise of CA-MRSA in many areas, clindamycin is also an appropriate first-line option. In older children and adolescents, anaerobic bacteria should be suspected in cases of cervical lymphadenitis associated with gingival infections or dental abscesses. In these cases, amoxicillin–clavulanate or clindamycin provide anaerobic coverage in addition to gram-positive coverage. Cervical lymphadenitis can be managed on an outpatient basis for most children who are well-appearing, well-hydrated, and have no evidence of abscess. Hospital admission for intravenous (IV) antibiotics should be considered in infants, ill-appearing children, children who have fluctuant nodes or associated cellulitis, and patients who have failed outpatient treatment. IV antibiotic choices include cefazolin, oxacillin, and ampicillin-sulbactam. In regions with a high prevalence of CA-MRSA, clindamycin or vancomycin provides adequate coverage. The total treatment course should be 10 to 14 days. If there is no response to antibiotic treatment within 48 to 72 hours or clinical worsening, the next steps include evaluation for abscess formation. Ultrasound is useful to detect the presence and extent of an abscess if lymph node fluctuance is not obvious by examination. Surgeons may request a computed tomography (CT) scan before performing an incision and drainage to obtain more detailed imaging of adjacent and deep structures that may not be seen on ultrasound. However, ultrasound offers the advantage of avoiding radiation exposure. Aspirated or drained material from a suppurative node should be sent for Gram stain and both aerobic and anaerobic bacterial culture. Acid-fast stain and culture for mycobacterium and fungi should be considered with the appropriate clinical picture.

In cases of subacute or chronic lymphadenitis, evaluation for tuberculosis, NTM, HIV, EBV, CMV, cat scratch disease, and toxoplasmosis should be considered based on history and physical examination findings. A PPD can be helpful in distinguishing tuberculous from NTM lymphadenitis. Serologic testing is available for B. henselae, T. gondii, EBV, and CMV. Polymerase chain reaction is the preferred diagnostic test for HIV. Toxoplasmosis and cat scratch disease are typically self-limited infections that do not require treatment. For patients with systemic disease secondary to B. henselae, treatment with azithromycin is an option. However, the role of antimicrobial therapy in cat scratch disease remains controversial. With NTM lymphadenitis, excisional biopsy of the node can provide a definitive diagnosis and is the preferred treatment. If surgery is not feasible because of the location of involved nodes, clarithromycin or azithromycin with ethambutol or rifampin should be considered. When the etiology of cervical lymphadenitis remains unclear after negative infectious workup results, patients should be monitored closely for systemic signs of disease. An excisional biopsy may be necessary to establish the diagnosis in cases of persistent lymphadenitis that do not respond to appropriate antibiotic treatment or when nodes are nontender and fixed to adjacent tissue suggestive of malignancy.

Etiology and Pathogenesis

Despite the widespread use of antibiotics for the treatment of tonsillitis and pharyngitis, peritonsillar abscess remains the most common deep infection of the head and neck. It occurs most frequently in older school-age children and adolescents. The peritonsillar space lies between the palantine tonsil and the superior pharyngeal constrictor muscle. Peritonsillar abscess is defined as a collection of pus between the tonsillar capsule, superior constrictor muscle, and palatopharyngeus muscle. It typically occurs in the superior pole of the tonsil. Peritonsillar abscess is generally preceded by tonsillitis or pharyngitis. When it occurs without preceding infection, a possible mechanism involves Weber’s glands, a group of salivary glands located superior to the tonsil. These glands clear the tonsillar area of debris, and if they become obstructed, an abscess can develop.

The retropharyngeal space is bordered posteriorly by the prevertebral fascia and anteriorly by the pretracheal fascia. Its superior border is the base of the skull, it extends inferiorly to the posterior mediastinum, and it communicates with the parapharyngeal space laterally. The retropharyngeal space contains two chains of lymph nodes that drain the nasopharynx, adenoids, and paranasal sinuses. Suppurative infection of these lymph nodes can result in abscess formation. Accordingly, retropharyngeal infections in children tend to be preceded by upper respiratory tract infections such as pharyngitis, tonsillitis, sinusitis, and cervical lymphadenitis. Retropharyngeal abscess occurs most commonly in preschool-age children. The reduced incidence of retropharyngeal infections in older children has been attributed to atrophy of these lymph nodes with age. In older children and adolescents, retropharyngeal abscess is more likely to result from trauma to the posterior pharynx, foreign body, or dental abscess.

The parapharyngeal (lateral pharyngeal) space is located in the lateral aspect of the neck. Structurally, it can be thought of as an inverted cone, with its base at the skull and apex at the hyoid bone. It can be further subdivided into an anterior and posterior compartment. The anterior compartment is near the tonsillar fossa and contains lymph nodes, connective tissue, and muscle. The posterior compartment consists of the carotid sheath, which protects the carotid artery, internal jugular vein, vagus nerve, cervical sympathetic trunk, and the ninth to twelfth cranial nerves. Sources of infection of the parapharyngeal space include pharyngitis, tonsillitis, parotitis, otitis media, mastoiditis, and dental infections. Parapharyngeal space infections most often arise via contiguous spread from a peritonsillar or retropharyngeal abscess.

Clinical Presentation and Differential Diagnosis

Patients with peritonsillar or retropharyngeal abscess present with fever, severe sore throat, neck pain, odynophagia, and decreased oral intake. Throat pain is more severe on the affected side and is often referred to the ipsilateral ear. Other associated findings include trismus, cervical lymphadenopathy, and pooling of saliva or drooling. With peritonsillar abscess, the physical examination usually reveals a patient with a partially opened mouth speaking in a muffled or “hot potato” voice. The oropharynx is erythematous with fullness or bulging of the superior pole of the tonsil. The uvula and tonsil may be deviated to the opposite side by the abscess (Figure 87-4). With retropharyngeal abscess, the physical examination may reveal neck swelling or torticollis. Bulging of the posterior pharyngeal wall lateral to the midline is suggestive of retropharyngeal abscess but is not consistently present. If left untreated, a peritonsillar or retropharyngeal abscess can spread through the deep tissues and produce complications such as airway compromise, mediastinitis, thrombophlebitis, and aspiration pneumonia if rupture occurs.

Figure 87-4 Peritonsillar abscess (quinsy).

The clinical manifestations of parapharyngeal infections can be subtle and depend on whether the anterior or posterior compartment is involved. Infections of either compartment can be associated with systemic toxicity, fever, cervical lymphadenopathy, and parotid gland swelling. The key clinical features of parapharyngeal abscess in the anterior compartment include odynophagia, trismus, and pain involving the ipsilateral side of the neck and jaw. On physical examination, there is induration and swelling below the angle of the mandible and medial displacement of the lateral pharyngeal wall and posterior tonsillar pillar. If swelling occurs in the area of the larynx or epiglottis, stridor and respiratory distress may be present. Posterior compartment involvement produces signs of sepsis with minimal trismus or pain. Swelling of the pharyngeal wall can be missed on oropharyngeal examination when it is deep to the palatopharyngeal arch. In these cases, the development of neurologic or vascular complications secondary to involvement of structures in the posterior compartment may lead to the diagnosis. Abscess in the posterior compartment may result in unilateral tongue paresis, vocal cord dysfunction, facial nerve weakness, Horner’s syndrome, hemorrhage from carotid artery erosion, or internal jugular vein thrombosis (Lemierre’s syndrome). In addition, intracranial complications such as meningitis, brain abscess, and thrombosis of the cavernous sinus may occur.

It can be difficult to differentiate between the early findings of peritonsillar, retropharyngeal, and parapharyngeal infections. Therefore, these diagnoses should all be considered in the differential diagnosis of deep neck infections. Patients with retropharyngeal or parapharyngeal abscesses may be misdiagnosed with meningitis because of neck pain and stiffness. Other diagnostic considerations include epiglottitis secondary to the signs of drooling and respiratory distress and laryngotracheobronchitis if the patient presents with stridor. The differential diagnosis of peritonsillar abscess includes severe tonsillopharyngitis and peritonsillar cellulitis. The lack of trismus and fluctuance in tonsillopharyngitis help to distinguish it from a peritonsillar abscess. It can be difficult to distinguish peritonsillar cellulitis from peritonsillar abscess clinically; however, with peritonsillar cellulitis, the uvula usually remains in the midline, and there is a lack of purulent material during a needle aspiration. A list of other differential diagnoses appears in Box 87-3.

Evaluation and Management

Laboratory evaluation is not necessary to make the diagnosis of deep neck infections, but it may help to assess the degree of illness and response to therapy. Leukocytosis with neutrophil predominance and elevated inflammatory markers are common, but these abnormalities are nonspecific. Associated bacteremia is uncommon, but a blood culture should be considered in an ill-appearing patient. Routine GABHS antigen test or throat culture should be done, keeping in mind the possibility of a carrier state with a positive result.

The diagnosis of peritonsillar abscess can usually be made clinically and is confirmed by a collection of pus at the time of drainage. A lateral neck radiograph may be obtained initially to exclude epiglottis and retropharyngeal abscess. In the case of retropharyngeal and parapharyngeal abscess, definitive diagnosis is established with radiographic studies. A lateral soft tissue radiograph of the neck may show widened prevertebral soft tissues and the presence of air-fluid levels within the retropharyngeal space. When retropharyngeal infection is present, the prevertebral soft tissue measures more than half the width of the adjacent vertebral body. The prevertebral space can appear falsely widened during neck flexion or with crying. Therefore, proper technique including imaging during inspiration and with the neck fully extended is essential. The most useful imaging modality for deep neck infections is a CT scan, which can define the source and extent of infection and determine whether there is abscess formation verses cellulitis or phlegmon. Magnetic resonance imaging (MRI) is another imaging option and avoids the irradiation that accompanies CT scan. However, sedation is typically required for young children, and the risk of sedating a child with potential airway compromise must be considered.

Aggressive monitoring and management of the airway is the most urgent and critical aspect of care for deep neck infections followed by appropriate antibiotic treatment and surgical drainage when necessary. There is a trend toward conservative early medical management with IV antibiotics for 24 to 48 hours when imaging is consistent with phlegmon, fluid collections are small, and there is no airway compromise. If there is worsening of clinical status or a suboptimal response to appropriate antibiotics, incision and drainage are necessary. Mature abscesses require surgical drainage. In the case of peritonsillar abscess, drainage is performed by either needle aspiration or incision and drainage.

Peritonsillar, retropharyngeal, and parapharyngeal abscesses tend to be polymicrobial in nature, consisting of both aerobic and anaerobic organisms. Empiric therapy should include coverage for S. pyogenes; non–group A streptococcus; S. aureus; and respiratory anaerobes such as Prevotella, Bacteroides, and Peptostreptococcus spp. Treatment failure with penicillin monotherapy because of the emergence of β-lactamase production among oral anaerobes has changed the preferred treatment to broader spectrum antibiotics. In areas where S. aureus remains susceptible to methicillin, ampicillin–sulbactam is appropriate. In areas with increased prevalence of CA-MRSA, antibiotic choices include clindamycin and vancomycin. IV therapy should be continued until the patient is afebrile with improvement in symptoms and resolution of any airway compromise. Oral therapy should be continued to complete a 14-day course. Appropriate oral regimens include amoxicillin–clavulanate, clindamycin, or linezolid. The use of steroids remains controversial, and there is not a clear role for them in the treatment of deep neck infections.

Etiology and Pathogenesis

The anatomy of the eye and its contiguous structures play an important role in the pathogenesis of periorbital and orbital cellulitis. The orbital septum is a fibrous tissue that extends from the periosteum of the superior and inferior orbital rims and reflects into the upper and lower eyelids. The orbital septum protects the periorbital area from the paranasal sinuses and provides a barrier to the spread of infection from the periorbital area into the orbit. Periorbital cellulitis most commonly arises from secondary bacterial infection of soft tissue injuries to the face or eyelids such as lacerations or insect bites or from spread of local infection such as conjunctivitis, dacryocystitis, or hordeolum. Periorbital cellulitis can also develop secondary to hematogenous spread of nasopharyngeal pathogens to the periorbital tissues. In addition, periorbital swelling can occur with acute sinusitis as a result of inflammatory edema because of poor venous drainage.

In contrast to the periorbital area, the orbit is surrounded by the paranasal sinuses. Many of the bony walls of the sinuses are thin and porous and allow spread of infection into the orbit. Orbital cellulitis most commonly results from extension of sinusitis with the ethmoid sinuses involved most frequently (Figure 87-5). Pathogens may also gain access to the orbit through direct trauma from a fracture or foreign body. In addition, spread of infection from adjacent structures can occur, such as an odontogenic infection extending into the maxillary sinus and subsequently into the orbit. Infection can also travel through the valveless venous system that drains the orbit and sinuses. These veins drain into the cavernous sinus, which can allow hematogenous spread of sinus infections into the orbit and result in complications such as thrombosis of the cavernous sinus, compression of the optic nerve, meningitis, or intracranial abscess.

Figure 87-5 Orbital spread of sinus infection.

Clinical Presentation and Differential Diagnosis

Periorbital and orbital cellulitis are both characterized by unilateral eyelid erythema, edema, induration, and tenderness. Only orbital cellulitis is associated with proptosis, impairment of extraocular movements, pain with extraocular movements, chemosis, or decreased visual acuity. The presence of fever or toxic appearance is variable, but both are more common with orbital cellulitis. Tearing may occur, but significant conjunctival injection and purulent drainage are not common unless there is associated conjunctivitis. Because the majority of patients with orbital cellulitis have concomitant sinusitis, a history of a recent upper respiratory tract infection or symptoms of sinusitis such as headache or sinus tenderness may be present (see Chapter 33). The clinician should inquire about recent trauma, insect bites, and skin or eye infections.

Several noninfectious conditions can present with eyelid swelling and should be considered in the differential diagnosis of periorbital and orbital cellulitis. Allergic reactions may cause acute eyelid swelling but typically are pruritic and bilateral and do not exhibit tenderness. Blunt trauma can cause unilateral periorbital swelling, ecchymosis, and tenderness to the eyelid. Historical information will help to differentiate trauma from infection. Hypoalbuminemia can cause eyelid swelling secondary to edema, but periorbital swelling tends to be bilateral, nontender, and without erythema. Other causes of periorbital swelling include chemical irritation, chalazion, dacryocystitis, and conjunctivitis. The differential diagnosis of orbital cellulitis also includes conditions that cause orbital inflammation. Orbital pseudotumor, an autoimmune inflammation of the orbital tissues, presents with eyelid swelling, pain, and decreased extraocular movements. These patients are typically afebrile, and CT scan reveals an intraorbital mass and no evidence of sinusitis. Intraocular tumors such as retinoblastoma and rhabdomyosarcoma usually cause gradual onset of proptosis without evidence of inflammation. Other conditions that may present similarly to orbital cellulitis include a subperiosteal hematoma and a ruptured dermoid cyst.

Evaluation and Management

Most cases of periorbital cellulitis can be diagnosed clinically. A CT scan should be performed in any patient with suspected orbital cellulitis to evaluate the extent of infection in the orbit, detect coexisting sinus disease, and identify an orbital or subperiosteal abscess (Figure 87-6). Leukocytosis with neutrophil predominance is often present in patients with periorbital and orbital cellulitis, so obtaining a complete blood count does not necessarily help to differentiate between the two diagnoses. Inflammatory markers are usually elevated, but these tests are neither sensitive nor specific. Blood cultures are typically negative but worth considering in an ill-appearing patient. Drainage aspirates of sinuses or abscesses associated with orbital cellulitis should be sent for culture when surgery is indicated.

Figure 87-6 Orbital cellulitis.

Most cases of periorbital cellulitis can be safely managed on an outpatient basis with oral antibiotics and close follow-up. Hospitalization and IV antibiotics should be considered in patients who are younger than 1 year old, toxic appearing, cannot tolerate oral antibiotics, or failed outpatient management. All patients with suspected orbital cellulitis require hospitalization for IV antibiotics and close observation for progression of symptoms by ophthalmology. If CT scan demonstrates sinus disease as a likely etiology, an otolaryngologist should be consulted because surgical drainage may be necessary. If there is no improvement after 24 to 48 hours of IV antibiotics or if there is worsening of clinical status at any time, repeat imaging to assess for abscess formation may be necessary to determine if surgery is required.

Antibiotic choices should be aimed at the most likely pathogens. For periorbital cellulitis secondary to trauma or adjacent soft tissue infection, antibiotic therapy should be targeted at S. aureus and S. pyogenes. Amoxicillin–clavulanate is an appropriate oral antibiotic. Because of the continuing rise of CA-MRSA in many areas, clindamycin is an alternative. Children who are hospitalized should receive IV ampicillin–sulbactam or clindamycin. The duration of treatment should be a total of 10 to 14 days. For orbital cellulitis, antibiotic therapy should be aimed at respiratory pathogens originating from the paranasal sinuses, including Streptococcus pneumoniae, nontypable Haemophilus influenzae, Moraxella catarrhalis, and anaerobes in addition to S. aureus and S. pyogenes. Ampicillin–sulbactam is an appropriate choice with a high dose of ampicillin to cover resistant S. pneumoniae. Clindamycin can be added to ampicillin–sulbactam for CA-MRSA coverage. A third-generation cephalosporin with clindamycin added for broader CA-MRSA and anaerobic coverage is another reasonable option. The total duration of antibiotic treatment is 14 to 21 days. For children who are admitted to the hospital, discharge criteria include resolving clinical symptoms with improved ophthalmologic examination, afebrile for 24 hours, and able to tolerate oral antibiotics.

Future Directions

With the continuing rise of CA-MRSA and potential development of other resistant bacterial strains, empirical antibiotic therapy for infections of the head and neck will continue to be challenging. The trend toward more conservative management of head and neck infections with a trial of IV antibiotics before attempting incision and drainage places additional significance on initial antibiotic choices. In addition, more randomized, controlled studies are necessary to delineate if there is a role for steroids in the treatment of deep neck infections. Furthermore, as awareness continues to increase regarding radiation exposure via imaging with CT scan, the use of other imaging modalities such as ultrasound and MRI to diagnose infections of the head and neck and follow progression will likely increase.